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5-Azacytidine

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Peggy J Farnham – One of the best experts on this subject based on the ideXlab platform.

  • 5-Azacytidine treatment reorganizes genomic histone modification patterns
    Epigenetics, 2010
    Co-Authors: Vitalina M. Komashko, Peggy J Farnham

    Abstract:

    Methylation of DNA in combination with histone modifications establishes an epigenetic code that ensures the proper control of gene expression. Although DNA methyltransferases have been shown to interact with histone methyltransferases such as EZH2 (which methylates histone H3 on lysine 27) and G9a (which methylates histone H3 on lysine 9), the relationship between DNA methylation and repressive histone marks has not been fully studied. In cancer cells, promoters of genes are often aberrantly methylated. Accordingly, 5-Azacytidine (a DNA demethylating drug) is used for treating patients with myelodysplastic syndrome. However, no genome-scale studies of the effects of this drug have been reported. In this work, we report the effects of 5-Azacytidine on global gene expression and analyze ~24,000 human promoters using ChIP-chip to determine how 5-Azacytidine treatment effects H3K27me3 and H3K9me3 levels. We found that (1) 5-Azacytidine treatment results in large changes in gene regulation with distinct funct…

  • 5-Azacytidine treatment reorganizes genomic histone modification patterns
    Epigenetics, 2010
    Co-Authors: Vitalina M. Komashko, Peggy J Farnham

    Abstract:

    Methylation of DNA in combination with histone modifications establishes an epigenetic code that ensures the proper control of gene expression. Although DNA methyltransferases have been shown to interact with histone methyltransferases such as EZH2 (which methylates histone H3 on lysine 27) and G9a (which methylates histone H3 on lysine 9), the relationship between DNA methylation and repressive histone marks has not been fully studied. In cancer cells, promoters of genes are often aberrantly methylated. Accordingly, 5-Azacytidine (a DNA demethylating drug) is used for treating patients with myelodysplastic syndrome. However, no genome-scale studies of the effects of this drug have been reported. In this work, we report the effects of 5-Azacytidine on global gene expression and analyze ~24,000 human promoters using ChIP-chip to determine how 5-Azacytidine treatment effects H3K27me3 and H3K9me3 levels. We found that (1) 5-Azacytidine treatment results in large changes in gene regulation with distinct functional categories of genes showing increased (e.g. C2H2 zinc finger transcription factors) and decreased (e.g. genes involved in regulation of mitochondria and oxidoreductase activity) levels; (2) most genes that show altered expression are not regulated by promoters that display DNA methylation prior to the treatment; (3) certain gene classes switch their repression mark upon treatment with 5-Azacytidine (from H3K27me3 to H3K9me3 and vice versa); and (4) most changes in gene expression are not due to relief of repression mediated by DNA or histone methylation.

Vitalina M. Komashko – One of the best experts on this subject based on the ideXlab platform.

  • 5-Azacytidine treatment reorganizes genomic histone modification patterns
    Epigenetics, 2010
    Co-Authors: Vitalina M. Komashko, Peggy J Farnham

    Abstract:

    Methylation of DNA in combination with histone modifications establishes an epigenetic code that ensures the proper control of gene expression. Although DNA methyltransferases have been shown to interact with histone methyltransferases such as EZH2 (which methylates histone H3 on lysine 27) and G9a (which methylates histone H3 on lysine 9), the relationship between DNA methylation and repressive histone marks has not been fully studied. In cancer cells, promoters of genes are often aberrantly methylated. Accordingly, 5-Azacytidine (a DNA demethylating drug) is used for treating patients with myelodysplastic syndrome. However, no genome-scale studies of the effects of this drug have been reported. In this work, we report the effects of 5-Azacytidine on global gene expression and analyze ~24,000 human promoters using ChIP-chip to determine how 5-Azacytidine treatment effects H3K27me3 and H3K9me3 levels. We found that (1) 5-Azacytidine treatment results in large changes in gene regulation with distinct funct…

  • 5-Azacytidine treatment reorganizes genomic histone modification patterns
    Epigenetics, 2010
    Co-Authors: Vitalina M. Komashko, Peggy J Farnham

    Abstract:

    Methylation of DNA in combination with histone modifications establishes an epigenetic code that ensures the proper control of gene expression. Although DNA methyltransferases have been shown to interact with histone methyltransferases such as EZH2 (which methylates histone H3 on lysine 27) and G9a (which methylates histone H3 on lysine 9), the relationship between DNA methylation and repressive histone marks has not been fully studied. In cancer cells, promoters of genes are often aberrantly methylated. Accordingly, 5-Azacytidine (a DNA demethylating drug) is used for treating patients with myelodysplastic syndrome. However, no genome-scale studies of the effects of this drug have been reported. In this work, we report the effects of 5-Azacytidine on global gene expression and analyze ~24,000 human promoters using ChIP-chip to determine how 5-Azacytidine treatment effects H3K27me3 and H3K9me3 levels. We found that (1) 5-Azacytidine treatment results in large changes in gene regulation with distinct functional categories of genes showing increased (e.g. C2H2 zinc finger transcription factors) and decreased (e.g. genes involved in regulation of mitochondria and oxidoreductase activity) levels; (2) most genes that show altered expression are not regulated by promoters that display DNA methylation prior to the treatment; (3) certain gene classes switch their repression mark upon treatment with 5-Azacytidine (from H3K27me3 to H3K9me3 and vice versa); and (4) most changes in gene expression are not due to relief of repression mediated by DNA or histone methylation.

Usama Wissa – One of the best experts on this subject based on the ideXlab platform.

  • High-Risk Myelodysplastic Syndromes: Chemotherapy, Transplantation, and Beyond
    Current Hematologic Malignancy Reports, 2010
    Co-Authors: Usama Gergis, Usama Wissa

    Abstract:

    Allogeneic hematopoietic cell transplantation (HCT) has curative potential for patients with myelodysplastic syndromes (MDS), though with considerable nonrelapse mortality and morbidity. The International Prognostic Scoring System, despite its confines, remains a widely used tool guiding treatment decisions in MDS. The two hypomethylating agents, 5-Azacytidine (azacitidine) and 5-aza-2-deoxycytidine (decitabine), are both effective in high-risk MDS, but about 50% of high-risk MDS patients fail to achieve a meaningful response, and these agents offer only a modest survival benefit, with a median response duration of 13 months. The more recent proposed risk models of MDS, as well as modern transplant strategies and expanded alternative donor sources, have helped to increase the number of patients offered curative treatment. As both drug therapy and HCT modalities evolve, treatment decisions are certain to become more complex. Current therapeutic options should view the hypomethylating agents as a way to optimize disease response before (and possibly after) HCT.